The K (capsular or envelope) antigens of Enterobacteriaceae lie exterior to the trilamellar outer membrane and have been implicated in the pathogenicity and invasiveness of certain strains of Escherichia Coli and Klebsiella. Only one E. coli K antigen (K1), however, has been shown to be a specific virulence factor in septecemic human disease (neonatal meningitis); and there is little information on the K types causing nosocomial gram negative bacillemia and the protective role of anti-K antibodies. In a prospective study of gram negative rod bacteremia, we observed that 40 percent of E. coli demonstrated absolute or relative resistance to phagocytosis in both patients and normal serum and preliminary evidence suggests that resistance to phagocytosis may be related to presence of specific K antigens or K antigen content. A major goal of this study will be immunochemical separation and electrophoresis purification of certain K antigens which will lead to improved methods for K typing E. coli to complement well established Klebsiella typing techniques. Availability of specific antigens and antibody will permit assessment of resistance to phagocytosis as a property of specific K type or content. Whether "resistance" is related to deficiencies in heat stable opsonins (antibodies) against O or K antigens or impaired complement activation, particularly of the "alternate" pathway, will be explored using specific antibodies quantitated by sensitive radiometric binding techniques. Because some K antigens cross react with antigens of Streptococcus pneumoniae, investigation of cross reacting antibodies in in vitro phagocytosis thus may give some indication of the potential protective impact of pneumococcal immunization on some types of gram negative rod septicemia. Study of the phenomena of resistance to phagocytosis of certain K types may give insight into the pathogenesis of some of the commonly occurring gram negative bacillary infections and rational approaches to their control by immunoprophylaxis.